AB0168 IMBALANCE IN THE TAXONOMIC COMPOSITION OF GUT MICROBIOTA IN TAKAYASU ARTERITIS
Authors: T. Shirai, S. Watanabe, N. Shinozaki, K. Baba, H. Yamasaki, T. Ishii, H. Fujii
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Takayasu arteritis (TAK) is one form of the large vessel vasculitis and predominantly affects young female. TAK sometimes coexists with other inflammatory diseases which include ulcerative colitis (UC) and spondyloarthropathy. Recent evidences revealed close genetic background between TAK and these diseases, and we found the common autoantibodies against endothelial protein C receptor among TAK and UC. These evidences suggest the common underlying pathophysiology among these diseases. UC and spondyloarthropathy are known to be associated with dysbiosis. Therefore, the involvement of dysbiosis in the pathogenicity of TAK is possible. However, little is known regarding the composition of gut microbiota in TAK. <h3>Objectives</h3> This study aimed to investigate whether there existed the imbalance in the taxonomic composition of gut microbiota in TAK. <h3>Methods</h3> 31 patients with TAK who satisfied the classification criteria of American College of Rheumatology 1990 and 31 background-matched healthy controls (HC) were included in this study. Feces were collected from each individual, and fecal microbial DNA was isolated. 16S rRNA gene amplicon sequencing was performed to analyze the microbiota. Microbial richness and β-diversity were compared among HC and TAK, and the differences in the abundant taxa were analyzed by the LEfSe algorithm. <h3>Results</h3> The clinical background of each group was as follows; the mean age, 41 years; female, 87%. The disease activity of TAK was assessed using the Indian Takayasu arteritis score (ITAS)-A, and 17% were in an active disease status when they collected feces. Then, 16S rRNA gene amplicon sequencing was successfully performed using microbial DNA extracted from the collected feces. Microbial richness was compared between HC and TAK using the Shannon index, which revealed significant decrease of microbial richness in TAK patients (P=0.02). β-diversity between HC and TAK was next investigated, and approximately half of the patients with TAK were clearly separated from the clusters of HC. Therefore, the presence of dysbiosis in TAK was confirmed even in the condition in which most of patients with TAK were in inactive status. Analysis of composition of microbiomes (ANCOM) showed abundance of eight and 10 genera in TAK and HC, respectively with the cut-off of centered log ratio as 1. Cladograms showed changes in the microbiota, in which each level of phylum, class, order, family, and genus were related. Differential microbiota at the genus level were observed at a linear discriminant analysis threshold of &gt;2.0. Altered microbial genera in our study included enrichment of Streptococcus, Lactobacillus, Veillonella, Enterococcus, Dialister, Actinomyces, Sardovia, Sellimonas, Rothia, and Campylobacter. More numbers of genera were depleted in TAK, which included Bacteroides, Phascolarctobacterium, Dorea, Parasutterella, Barnesiella, and Acidaminococcus. Importantly, enrichment of oral bacteria species was documented in most of the patients with TAK. Among them, two cases were complicated with infectious endocarditis during the treatments with tocilizumab, suggesting the contribution of dysbiosis for such complication in TAK. <h3>Conclusion</h3> Significant imbalance of gut microbiota was observed in TAK. The diversity of fecal microbiota was reduced in TAK, and altered genera were relevant for the exacerbation of inflammation. Dysbiosis could be related to the exacerbation of inflammation and the complications in TAK. <h3>References</h3> [1]Mutoh T, Shirai T, et al. Identification of two major autoantigens negatively regulating endothelial activation in Takayasu arteritis. Nat Commun. 2020;11(1):1253. [2]Shirai T, Kakuta Y, Fujii H. Distinct Autoantibodies Against Endothelial Protein C Receptor in Ulcerative Colitis. Gastroenterology. 2021;161(5):1724-5. [3]Kakuta Y, Shirai T, et al. Novel Diagnostic Autoantibodies Against Endothelial Protein C Receptor in Patients With Ulcerative Colitis. Clin Gastroenterol Hepatol. 2021; 3565(21)01359-8. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.